Dimethylformamide → (2R)-2-{[2-(benzyloxy)-4-nitrophenoxy]methyl}oxirane

HRID 1259445Notes

Reaction equation

[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:10]=1[O-:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[K+].S(C1C=CC(C)=CC=1)(O[CH2:24][C@@H:25]1[O:27][CH2:26]1)(=O)=O.CN(C=O)C>O>[CH2:1]([O:8][C:9]1[CH:14]=[C:13]([N+:15]([O-:17])=[O:16])[CH:12]=[CH:11][C:10]=1[O:18][CH2:24][C@H:25]1[CH2:26][O:27]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 65 °C

Procedure

A 30 L jacketed reactor is charged with potassium 2-(benzyloxy)-4-nitrophenolate (1.31 kg, 4.62 mol), (R)-glycidyl tosylate (1.13 kg, 4.96 mol) and DMF (6.5 L). The resulting suspension is heated until an internal temperature of 65° C. is obtained, and is then stirred for 18 h. The solution is cooled to 20° C., and then water (2 L) is added over 30 min. The solution is seeded with 2 g of the desired product, and the addition of water is resumed (9 L over 1.25 h). The slurry is stirred for 2.5 h, and then collected by vacuum filtration. The reactor and filter cake are washed with water (5 L total) and suction dried to give the title compound (1370 g, 98%) as an off-white powder. LCMS (Standard Method): 2.74 min, 302 (M+H)−. 1H NMR (300 MHz, CDCl3) δ 7.89 (dd, J=2.6, 9.0 Hz, 1H), 7.81 (d, J=2.6 Hz, 1H), 7.48-7.34 (m, 5H), 6.98 (d, J=8.8 Hz, 1H), 5.19 (s, 2H), 4.43 (dd, J=2.7, 11.5 Hz, 1H), 4.08 (dd, J=5.8, 11.5 Hz, 1H), 3.43-3.39 (m, 1H), 2.95-2.91 (m, 1H), 2.81-2.78 (m, 1H).

Workup

customis obtained
temperatureThe solution is cooled to 20° C.

Sources & evidence

ORD record: ord-d4b5e362e650481e92c5a1c05dfc0ff1
Source dataset: uspto-grants-2013_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08466296B2

Reaction notes

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